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Selective compartmentalization in condensin-depleted mitotic chromosomes [Hi-C II]

ABSTRACT: During mitosis, condensin activity is thought to disrupt interphase chromatin structures. Here, we utilize condensin-deficient mitotic chromosomes as a unique architectural platform to further investigate genome folding principles. Upon condensin loss, compartments progressively emerge in mitotic chromosomes. Euchromatin diverges into two different compartments A1 and A2, the former of which shows strong homotypic interactions while the latter exhibit reduced self-aggregation. Constitutive heterochromatin (B1) displays reduced level of compartmentalization and the normally inert facultative heterochromatin (B2) participates to compartmentalize the genome. Dynamically, A1 compartment is established remarkably fast with similarly efficient separation from B1 while reformation of B1 is delayed, implying that A1 self-attraction is the engine to compartmentalizalize the condensin-depleted mitotic chromosomes. Notified by the mitotic compartmentalization of B1 which lacks HP1 binding, we sought to explore the role of HP1 proteins in genome folding and demonstrat that HP1& are dispensible for chromatin structural restoration during cell divison. Our observations unveil delicate patterns and novel principles of genome compartmentalization that are otherwise hidden in interphase cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE247575 | GEO | 2023/11/22

REPOSITORIES: GEO

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Selective compartmentalization in condensin-depleted mitotic chromosomes [HiC-C]

Project description:During mitosis, condensin activity is thought to disrupt interphase chromatin structures. Here, we utilize condensin-deficient mitotic chromosomes as a unique architectural platform to further investigate genome folding principles. Upon condensin loss, compartments progressively emerge in mitotic chromosomes. Euchromatin diverges into two different compartments A1 and A2, the former of which shows strong homotypic interactions while the latter exhibit reduced self-aggregation. Constitutive heterochromatin (B1) displays reduced level of compartmentalization and the normally inert facultative heterochromatin (B2) participates to compartmentalize the genome. Dynamically, A1 compartment is established remarkably fast with similarly efficient separation from B1 while reformation of B1 is delayed, implying that A1 self-attraction is the engine to compartmentalizalize the condensin-depleted mitotic chromosomes. Notified by the mitotic compartmentalization of B1 which lacks HP1 binding, we sought to explore the role of HP1 proteins in genome folding and demonstrat that HP1& are dispensible for chromatin structural restoration during cell divison. Our observations unveil delicate patterns and novel principles of genome compartmentalization that are otherwise hidden in interphase cells.

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Project description:Background: Structural maintenance of chromosomes (SMC) complexes are central organizers of chromatin architecture throughout the cell cycle. The SMC family member condensin is best known for establishing long-range chromatin interactions in mitosis. These compact chromatin and create mechanically stable chromosomes. How condensin contributes to chromatin organization in interphase is less well understood. Results: Here, we use efficient conditional depletion of fission yeast condensin to determine its contribution to interphase chromatin organization. We deplete condensin in G2 arrested cells to preempt confounding effects from cell cycle progression without condensin. Genome-wide chromatin interaction mapping, using Hi-C, reveals condensin-mediated chromatin interactions in interphase that are qualitatively similar to those observed in mitosis, but quantitatively far less prevalent. Despite its low abundance, chromatin mobility tracking shows that condensin markedly confines interphase chromatin movements. Without condensin, chromatin behaves as an unconstrained Rouse polymer with excluded volume, while condensin constrains its mobility. Unexpectedly, we find that condensin is required during interphase to prevent ongoing transcription from eliciting a DNA damage response. Conclusions: In addition to establishing mitotic chromosome architecture, condensin-mediated long-range chromatin interactions contribute to shaping chromatin organization in interphase. The resulting structure confines chromatin mobility and protects the genome from transcription-induced DNA damage. This adds to the important roles of condensin in maintaining chromosome stability.

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